Flash Continuous Glucose Monitoring Utilization in Type 2 Diabetes

Frequent self-monitoring of blood glucose (SMBG) can reduce the risk of hypoglycemia and improve glycemic control in patients with diabetes.¹ Continuous glucose monitoring (CGM) has revolutionized the way patients can monitor their glucose.

The first continuous glucose monitoring (CGM) was approved by the FDA in 1999.² It was a “professional” type, meaning the patient was blinded to the glucose data collected and the information had to be downloaded in the health care provider’s office.²

In contrast, personal CGM enables patients to see the glucose information in real-time at home. A personal CGM system may remove the need for routine SMBG using the traditional finger sticking method.³

There are 2 types of personal CGM systems: real-time continuous glucose monitoring (rtCGM) and flash continuous glucose monitoring (FCGM).³ FCGM is also known as the intermittently scanned CGM,³ whereas rtCGM automatically sends user glucose information in real-time.³ It also provides alerts and active alarms.³ Sensor-augmented insulin pump therapy utilizes rtCGM.³

The first personal CGM was an rtCGM,² which was approved by FDA in 2001.⁴ It was worn as a wristwatch, which was eventually discontinued due to various concerns, including inaccurate measurements.⁵ Currently, there are rtCGM available from 2 different manufacturers: Dexcom and Medtronic.⁶

FCGM provides similar glucose information to rtCGM, but it requires the user to scan the sensor to obtain information.³ It also lacks the options of alerts and alarms.³ There is 1 one type of FCGM available, which is the FreeStyle Libre FCGM.³

It was first introduced into the US market in 2017.² Patients need to scan the sensor at least every 8 hours to capture the entire 24-hour glucose information.³ If more than 8 hours pass between the scans, only the glucose information from the most recent 8 hours before the last scan will be available for review.³ FreeStyle Libre FCGM is approved by FDA for the management of diabetes in adult patients who are not pregnant or on dialysis.⁶

The convenience that comes with rtCGM is incorporated in its price as well, when compared with the price of FCGM.⁶ The first month of rtCGM using Dexcom or Medtronic for 1 patient can cost approximately $1000.⁶ FCGM is a much cheaper alternative, as continuous glucose monitoring for the first month using FCGM will be less than $200 in comparison.⁶ Therefore, FCGM can be a cost-effective option for patients, even with its limitations.

Most of the evidence for CGM use is in type 1 diabetes patients. Therefore, CGM is considered as “the standard of care” for patients with type 1 diabetes.³ However, the evidence is growing for CGM, including FCGM, for patients with type 2 diabetes.

EVIDENCE

Hemoglobin A1c (HbA1c) Reduction

The evidence is somewhat conflicting in whether FCGM leads to a reduction in hemoglobin A1c in type 2 diabetes. A multicenter, open-label randomized controlled trial was conducted by the manufacturer of the currently sole existing FCGM, Abbott, to assess flash glucose-sensing technology as a replacement for blood glucose monitoring for the management of insulin-treated type 2 diabetes (REPLACE trial).⁷

The study did not find any impact of FCGM on HbA1c.⁷ However, there is a meta-analysis that shows that 3 to 6 months of use of FCGM led to a reduction of 0.9 ± 0.05% (mean ± standard error [SE]) in HbA1c in patients with type 2 diabetes.⁸ The meta-analysis included 3 retrospective chart review studies with a total of 363 records.⁸

The patient population was adults on a basal-bolus insulin regimen with an average HbA1c of 8.9 ± 0.9% (mean ± standard deviation [SD]).⁸ There is another meta-analysis of 25 studies that showed a lower mean HbA1c reduction of —0.55% (95% confidence interval [CI] –0.70, –0.39).⁹ However, these studies included patients with type 1 diabetes as well.⁹

Indeed, there were 1049 adult patients with type 1 diabetes compared with 227 adult type 2 diabetics.⁹ However, there was no significant difference in the results between type 1 diabetes and type 2 diabetes.⁹ The baseline HbA1c determined the degree of change a patient had in the final HbA1c.⁹ For each percentage increase in the mean initial HbA1c from 6.6%, the analysis found the final HbA1c to reduce by 0.31% (95% CI −0.43 to −0.19).⁹

A meta-analysis with 12 studies that included 2173 patients with type 1 diabetes or type 2 diabetes on insulin regimen found a reduction of —0.26% (95% CI −0.43 to −0.09) in HbA1c with the utilization of FCGM.¹⁰ However, the analysis did not find a significant difference in the final HbA1c when the studies with only type 2 diabetes patients were considered (−0.51% [95% CI −1.03 to 0.01]).¹⁰ There was even less of a difference when FCGM was compared with SMBG (−0.22% [95% CI −0.72 to 0.28]).¹⁰

A systematic review of 9 randomized controlled trials concluded that some subgroups of patients with type 2 diabetes may experience a decrease in HbA1c with FCGM utilization.¹¹ These are patients with uncontrolled type 2 diabetes, on multiple daily insulin injections, and 65 years of age or younger.¹¹

Time in Hypoglycemia Reduction

Although the REPLACE trial was unable to show any impact of FCGM on HbA1c, the study found that FCGM led to a 43% reduction in time spent in hypoglycemia (<70 mg/dL).⁷ The reduction was 0.47 ± 0.13 (mean ± SE) hours per day compared with SMBG.⁷ FCGM also led to a 53% reduction in time spent in <55 mg/dL glucose.⁷

One of the previously mentioned meta-analyses with 12 studies found a decrease of 0.60 hours per day in time spent in hypoglycemia with the use of FCGM.¹⁰ However, the analysis did not report the comparative data of FCGM versus SMBG in decreasing the time spent in hypoglycemia.¹⁰

Cost Analysis

There is a UK perspective analysis of the estimated cost difference between FCGM and SMBG based on the observations in the REPLACE trial using UK National Health Service costs for different medical services.¹² FCGM would incur an additional cost of £585 annually per patient compared with 3 SMBG tests per day.¹²

However, FCGM led to a 41% reduction in emergency department visits, a 66% reduction in ambulance call-outs, and a 77% reduction in hospital admissions during the REPLACE trial.¹² Based on these numbers, FCGM would lead to an annual saving of £191 per patient compared with 3 SMBG tests per day.¹²

A prospective nationwide registry in the Netherlands also found that 1 year use of FCGM decreased annual diabetes-related hospital admission rate from 13.7% to 2.3% for patients with type 1 diabetes or type 2 diabetes.¹³ However, the difference did not meet statistical significance for type 2 diabetes patients alone despite the rate decreasing from 13% to 7.2%.¹³ Nevertheless, the study found that FCGM led to a statistically significant decrease in work absenteeism rate per 6 months from 19% to 6.1% in patients with type 2 diabetes.¹³

Patient Satisfaction

FCGM leads to more patient satisfaction compared to SMBG.¹⁴ A survey comparing 133 patients on FCGM with 83 patients on SMBG found that FCGM users had better ease of use, enjoyed more flexibility, and felt less restricted.¹⁴ SMBG users complained of measurement taking more time, being more worried, and considered the process a hassle and painful.¹⁴

Furthermore, patients on FCGM felt less frustrated with diabetes and less depressed.¹⁴ The article did not mention whether the patients surveyed had type 1 diabetes or type 2 diabetes. However, a systematic review that included patients with type 1 and type 2 diabetes concluded that FCGM led to higher patient satisfaction and lower diabetes distress compared with usual care.¹¹ A study of 101 patients with type 2 diabetes also found FCGM to be significantly more flexible for patients.¹⁵ Patients also stated that they would recommend FCGM to others with diabetes.¹⁵

Limitations

One limitation of CGM is its accuracy in hypoglycemia.³ FCGM has a mean absolute relative difference (MARD) of 24% when the glucose level is ≤70 mg/dL, while it has a MARD of only 9.7% overall.³ FCGM also has a high MARD of 19% (SD, 10%) when venous blood glucose changes at a rate >3 mg/dL per minute.¹⁶

Patients must verify FCGM readings with SMBG in these settings. FreeStyle recommends SMBG when glucose is changing at a rate >2 mg/dL per minute.¹⁷ There are various other conditions in which patients need to use SMBG to confirm FCGM reading. These include FCGM reading not matching symptoms being experienced, sensor reading not including a current glucose number or a trend arrow, during the first hour of wearing a sensor, etc.¹⁷

GUIDELINES

The American Diabetes Association’s (ADA) “Standards of Medical Care in Diabetes—2020” includes various recommendations involving FCGM.^18,19 The ADA has a level B recommendation (evidence from well-conducted cohort and case-control studies) for FCGM to be used in conjunction with insulin therapy in type 2 adult diabetes patients to lower HbA1c and/or reduce hypoglycemia for patients who are not meeting their glycemic goal.¹⁸

There are also 2 new recommendations in the 2020 update involving CGM.¹⁹ The ADA recommends a standardized report for all CGM devices called the Ambulatory Glucose Profile (AGP).¹⁹ AGP should include standardized CGM metrics per the 2019 international consensus, such as time in range (TIR), time below target, time above target, etc.²⁰

The other new recommendation is about TIR being an acceptable end point for clinical trials.¹⁹ Due to the risk of microvascular complications associated with TIR, it can be used as an assessment tool for glycemic control.¹⁹ Seventy percent of TIR (70-180 mg/dL) is strongly correlated with an HbA1c of approximately 7% per 2 prospective studies.¹⁹

Furthermore, time below target (<70 and <54 mg/dL) and time above target (>180 mg/dL) can be used to reevaluate a treatment regimen.¹⁹ The report from FreeStyle Libre FCGM provides these metrics.²¹

CONCLUSION

FCGM may reduce HbA1c and time spent in hypoglycemia for insulin-treated adult patients with type 2 diabetes. It can be cost saving when the decrease in medical resources utilization is considered and patients prefer using FCGM over SMBG.

Therefore, it can be a potential substitute for SMBG in adult patients with type 2 diabetes who require frequent glucose testing. The vast amount of information provided by this technology can aid health care professionals in the management of diabetes.

Despite FCMG’s shortcomings compared with rtCGM, its affordability makes it a prudent choice for patients.

About the Authors

Sayyem Akbar, PharmD, PhC, LT, U.S. Public Health Service, Clinical Pharmacist, Whiteriver Indian Hospital

L. Michelle Vaughn, PharmD, BCACP, BC-ADM, CDE, LCDR, U.S. Public Health Service, Clinical Pharmacist, PGY-2 Ambulatory Care Residency Program Director, Whiteriver Indian Hospital.

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